The invention relates to an ion source for a mass spectrometer and to a method of providing a source of ions for analysis. Mass spectrometers normally operate at low pressure and the present invention is particularly concerned with an ion source which operates at atmospheric pressure. Such ion sources include electrospray ion sources and atmospheric pressure chemical ionisation (APCI) ion sources.
Mass spectrometers have been used to analyse a wide range of materials, including organic substances, such as pharmaceutical compounds, environmental compounds and biomolecules. For mass analysis, it is necessary to produce ions of such sample compounds and biomolecules. Of particular use in the study of biological substances are mass spectrometers which have ion sources for creating ions of the sample compounds, where such ion sources operate at atmospheric pressure.
One such ion source is the electrospray ionisation (ESI) source which typically consists of a small tube or capillary through which a sample liquid is flowed. The sample liquid comprises the sample compounds and molecules to be analysed contained in a solvent. The capillary is maintained at a high potential difference relative to an adjacent surface. The liquid emerges from the tube and disperses into fine ionised droplets as a consequence of the high electric field at the tip of the capillary. The droplets are then desolvated by heating them to evaporate the solvent. Eventually, the ionised droplets become so small that they are unstable, whereupon they vaporise to form gaseous sample ions.
Another form of atmospheric pressure ion source is the atmospheric pressure chemical ionisation (APCI) ion source which uses a heated nebulizer to convert droplets of sample solution into the gaseous phase before ionisation. A corona discharge electrode is located adjacent to the nebulizer outlet. This ionises the surrounding gas and the nebulized solvent molecules. Since sample molecules generally have greater proton affinity than solvent molecules, collisions between them result in preferential ionisation of the sample molecules. In this way, gaseous sample ions are produced. ESI and APCI are complementary techniques, in that ESI is limited to charged or polar compounds, whereas APCI can be used for less polar compounds.
One problem with any technique involving droplets of sample solution is that despite the use of desolvation techniques, undesolvated droplets, dust and neutrals can enter the spectrometer producing a noise signal at the detector. Such particles can be prevented from entering the vacuum system of the mass spectrometer by, for example, using an opposing flow of dry gas ( e.g. nitrogen). However this solution is cumbersome and complex and involves the provision of a gas flow system and a supply of expensive pure gas.
Another approach is shown in U.S. Pat. No. 5,171,990, which shows an electrospray ion source in which the spray is directed off axis so that undesolvated ions do not enter the vacuum system. Similarly, U.S. Pat. No. 4,861,988 shows an electrospray ion source wherein the axis of the spraying capillary is offset from the axis of the sampling orifice to prevent sampling of large cluster ions.
U.S. Pat. No. 5,495,108 shows an electrospray/APCI mass spectrometer with orthogonal sampling to reduce vapour in the vacuum system and resultant noise. The spray is directed transversely across the sampling orifice, desolvated ions being electrostatically attracted into the mass spectrometer while solvent vapour and undesolvated ions to not enter the spectrometer region.
Van der Hoeven et al in J. Chromatog. A Vol. 712 (1995) pp. 211-218 discuss an electrospray interface adapted from a thermospray source, in which the longitudinal axis of the electrospray needle assembly, the entrance to the electrospray interface and the outlet to the vacuum pump which evacuates the interface are disposed generally along a first axis, the longitudinal axis of the mass spectrometer forming a second axis which is disposed transversely to the first axis, an electrostatic repeller electrode also being disposed along the second axis and directly opposite the entrance to the mass spectrometer. Neutrals and undesolvated ions should therefore tend to be evacuated directly by the pump, only required desolvated ions tending to be repelled into the mass spectrometer.
A disadvantage of any ion source system (such as U.S. Pat. Nos. 5,171,990 and 4,861,988) in which the sprayed sample is directed generally towards the spectrometer entrance, and there is a line of sight path between the location of ion generation and the entrance, is that some undesired particles can still enter the spectrometer. A further problem associated with line of sight sources is that of streaming. This is a consequence of the fluid dynamics of the system. When a gas flows through an aperture from an area of high pressure into an area of low pressure, a so called xe2x80x9cZone of silencexe2x80x9d forms around and downstream of the aperture. Inside this zone the gas molecules acquire a high velocity, the molecules following straight streamlines with the highest intensity being along the aperture axis. The closer the spectrometer entrance is to this axis, such as in a line of sight source, the more gas will stream through directly into the spectrometer, increasing the load on the vacuum system within the spectrometer.
On the other hand, in those systems, (e.g. Van der Hoeven et al) in which the sample ions are directly generally transversely to the spectrometer entrance, an electrostatic repeller is required to deflect desolvated ions into the Sass spectrometer.
In one aspect, the present invention provides an ion source for a mass spectrometer which operates at a low pressure comprising an atmospheric pressure sample ioniser operative at atmospheric pressure to provide a sample flow containing desired sample ions entrained with undesired gas and droplets, an interface chamber having an evacuation port, and a vacuum pump connected to the evacuator port to hold the interface chamber at a pressure intermediate atmospheric pressure and the operating pressure of the mass spectrometer, the interface chamber having an entrance orifice located to collect desired sample ions with entrained gas and droplets into the interface clamber from said sample flow of said sample ioniser said entrance orifice having a flow axis and forming a stream of gas into said interface chamber along said flow axis, and an exit orifice for sample ions to exit the interface chamber to the mass spectrometer, wherein the interface chamber is arranged to disrupt said stream of gas to provide a dead region within said chamber of no net gas flow direction and said exit orifice is located in said dead region.
Preferably, the interface chamber has a flow disrupting surface intersecting the flow axis of the entrance orifice. Then the interface channel may form a flow channel between the entrance orifice and the evacuation port and said flow disrupting surface is provided by a flow disrupting member in said flow channel.
The invention also provides an ion source for a mass spectrometer which operates at low pressure comprising an atmospheric pressure sample ioniser operative at atmospheric pressure to provide a sample flow containing desired sample ions entrained with undesired gas and droplets, an interface chamber having an evacuation port, and a vacuum pump connected to the evacuation port to hold the interface chamber at a pressure intermediate atmospheric pressure and the operating pressure of the mass spectrometer, the interface chamber having an entrance orifice located to collect desired sample ions with entrained gas and droplets into the interface chamber from said sample flow of said sample ioniser and an exit orifice for sample ions to exit the interface chamber to the mass spectrometer, wherein there is no line of sight path in the interface chamber between the entrance orifice and the exit orifice. Alternatively, the exit orifice may be in line of sight with said entrance orifice, wherein the line of sight is at least 30xc2x0 to said flow axis of the entrance aperture. Then, the entrance orifice may have a flow axis and form a stream of gas into said interface chamber along said flow axis, and the interface chamber may include flow disrupting means to disrupt said stream of gas to provide a dead region within said chamber of no net gas flow direction, said exit orifice being located in said dead region. Also, said interface chamber may form a flow channel between the entrance orifice and the evacuation port.
In a further aspect, she present invention provides an ion source for a mass spectrometer which operates at low pressure, comprising an atmospheric pressure sample ioniser operative at atmospheric pressure to provide a sample flow containing desired sample ions entrained with undesired gas and droplets, an interface chamber having an evacuation port, and a vacuum pump connected to the evacuation port to hold the interface chamber at a pressure intermediate atmospheric pressure and the operating pressure of the mass spectrometer, the interface chamber having an entrance orifice located to collect desired sample ions with entrained gas and droplets into the interface chamber from said sample flow of said sample ioniser, and an exit orifice for sample ions to exit the interface chamber to the mass spectrometer, the interface chamber defining a flow channel between the entrance orifice and the evacuation port, wherein the exit orifice is located out of said flow channel.
Preferably, the interface chamber further forms a side chamber to one side of said flow channel, said chamber containing a dead region in which there is no net gas flow direction, and said exit orifice is located in said side chamber to collect sample ions from said region.
In a still further aspect, the invention also provides an ion source for a mass spectrometer which operates at low pressure, comprising an atmospheric pressure sample ioniser operative at atmospheric pressure to provide a sample flow containing desired sample ions entrained with undesired gas and droplets, an interface chamber having an evacuation port, and a vacuum pump connected to the evacuation port to hold the interface chamber at a pressure intermediate atmospheric pressure and the operating pressure of the mass spectrometer, the interface chamber having an entrance orifice located to collect desired sample ions with entrained gas and droplets into the interface chamber from said sample flow of said sample ioniser, an exit orifice for sample ions to exit the interface chamber to the mass spectrometer, and flow splitting means arranged to favour the collection of sample ions from the interface chamber by said exit orifice, wherein said flow splitting means comprises means providing in said interface chamber a dead region of no net gas flow direction, said exit orifice being located in said dead region.
Preferably, the interface chamber defines a flow channel between the entrance orifice and the evacuation port and said flow splitting means comprises a side chamber in said interface chamber, said side chamber being located to one side of said flow channel and containing said dead region.
In preferred examples, the ion source includes a flow disrupting member in said flow channel.
Indeed, in a yet further aspect the present invention provides an ion source for a mass spectrometer which operates at low pressure comprising an atmospheric pressure sample ioniser operative at atmospheric pressure to provide a sample flow containing desired sample ions entrained with undesired gas and droplets, an interface chamber having an evacuation port, and a vacuum pump connected to the evacuation port to hold the interface chamber at a pressure intermediate atmospheric pressure and the operating pressure of the mass spectrometer, the interface chamber having an entrance orifice located to collect desired sample ions with entrained gas and droplets into the interface chamber from said sample flow of said sample ioniser, said entrance orifice having a flow axis, and an exit orifice for sample ions to exit the interface chamber to the mass spectrometer, the interface chamber defining a flow channel between the entrance orifice and the evacuation port, wherein the ion source includes a flow disrupting member in said flow channel to create a dead region of no net gas flow direction in the interface chamber, and the exit orifice is located to be spaced from said flow axis of the entrance orifice to collect sample ions from said dead region.
Preferably, said interface chamber further forms a side chamber to one side of said flow channel, said dead region extending into said side chamber and said exit orifice being located in said side chamber.
It is normal practice to include an interface chamber between the atmospheric pressure region in which sample ions are produced and the low pressure chamber of the mass spectrometer itself. The interface chamber is strongly pumped to keep the pressure of the interface chamber relatively low (but higher than the mass spectrometer pressure) and to relieve the load on the evacuation system of the mass spectrometer.
Because of the substantial pressure difference between the atmospheric pressure region and the interior of the interface chamber, the gas with sample ions entering the chamber forms a high velocity jet immediately inside the entrance interface. This in turn forms a stream or flow of gas within the interface chamber substantially along the flow axis of the entrance orifice. By arranging for the exit orifice of the interface chamber to be in a dead region of the chamber where there is no net gas flow, or at least well out of the flow channel between the entrance orifice and the evacuation port of the interface chamber, the tendency of larger droplets and other particles entrained with the incoming gas to pass directly through the exit orifice and on through the mass spectrometer to the ion detector, is greatly reduced if not eliminated. The presence of means to disrupt the incoming flow of gas into the interface chamber can enhance the presence of sample ions in the dead region, thereby improving the sensitivity of the instrument.
The flow disrupting member may comprise a pin projecting into said flow channel. The pin may have a transverse dimension perpendicular to the flow channel which is greater than the aperture size of the entrance orifice.
The source may include a flow restrictor disposed in the flow channel between the entrance orifice and the disrupting member. There may also be flow control means to control the rate of flow from the interface chamber through the evacuation port.
The flow disrupting member is provided to disrupt the streamlined flow of gas from the entrance aperture of the interface chamber and to ensure distribution of the ions entering the interface chamber throughout the volume of the chamber, and especially in the dead region within the interface chamber from which sample ions are drawn through the exit orifice into the mass spectrometer.
Importantly, the entire interface chamber, including not only the entrance and exit orifices, but also the flow disrupting member, is preferably held at the same electric potential, so that there is no acceleration of ions within the interface chamber. Ions flow from the interface chamber into the mass spectrometer due to the pressure differential between the interface chamber and the lower pressure spectrometer chamber. Because the exit aperture is located in a part of the interface chamber where there is no organised flow of gas, the ions and any neutral molecules and particles enter the spectrometer region through the exit aperture of the interface chamber at thermal energies.
The arrangement of the interface chamber and the disrupting member may be such as to minimise the proportion of undesolvated droplet ions and unwanted cluster ions in the region of the interface chamber from which sample ions are drawn through the exit is aperture. However, any neutrals or undesolvated droplets entering the mass spectrometer through the exit orifice, do so with no substantial net velocity, and so the probability of any such neutral or droplet proceeding through the spectrometer to the ion detector is very much reduced.
Further, unwanted cluster ions entering the mass spectrometer through the exit orifice, experience an accelerating electric field. Because of the reduced pressure, and the increased mean free path in the mass spectrometer region, the accelerated cluster ions experience energetic collisions in this region sufficient to break up the clusters.
Preferably, said entrance orifice has a first flow axis and said exit orifice has a second flow axis, and said first and second flow axes are spaced apart and arranged so as not to intersect within the interface chamber. This arrangement minimises the possibility of direct flight paths from the entrance orifice to the exit orifice of the interface chamber.
Conveniently, said first and second flow axes are parallel.
In preferred arrangements, there is no line of sight path in the interface chamber between the entrance orifice and the exit orifice.
The invention also provides a method of providing a source of ions for mass analysis of desired sample ions at a low mass analysis pressure, comprising the steps of forming a sample flow at atmospheric pressure containing desired sample ions entrained with undesired gas and droplets, skimming desired sample ions with entrained gas and droplets from said sample flow into an interface chamber evacuated to an intermediate pressure below atmospheric and above the mass analysis pressure, providing in said interface chamber a region of stagnant or turbulent gas flow, and skimming desired sample ions from said region for mass analysis.